title: Interaction of cyclic mechanical stretch and toll-like receptor 4-mediated innate immunity in rat alveolar type II cells.
abstract: OBJECTIVE
  In cases of infection-induced acute lung injury, mechanical ventilation might be necessary to maintain oxygenation. Although low tidal volume ventilation is applied, alveolar over-distension may occur and result in ventilator-induced lung injury. In this study, we investigate (i) the influence of lipopolysaccharide (LPS) stimulation on high-amplitude stretching; and (ii) the effect of stretching on LPS-mediated immune response in isolated rat alveolar type II cells.
  
  
  METHODS
  Type II cells were incubated with LPS and stretched for 24 h on elastic membranes. Initially we examined apoptosis and lactic acid dehydrogenase release in LPS-treated stretched cells. Furthermore we determined toll-like receptor (TLR) 4 expression, TLR4 signalling by analysis of nuclear factor κB (NF-κB) activation and the secretion of inflammatory cytokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-2, interleukin-1 beta, tumour necrosis factor alpha).
  
  
  RESULTS
  Our results show that LPS increases apoptosis and cytotoxicity in high amplitude stretched cells. Stretching and LPS activate NF-κB. The LPS influence is the prevailing one while no synergistic effects were observed by additional stretching. LPS stimulates an increased secretion of the inflammatory mediators only. Stretching had no influence on cytokines secretion.
  
  
  CONCLUSIONS
  We conclude that activation of TLR4 mediated immunity intensifies cell damage caused by stretching whereas in return stretching had no influence on TLR4 mediated innate immunity.
authors.affiliation: Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kuhn
authors.forename: Katja
authors.initials: K
authors.lastname: Petzold
authors.forename: Stefan
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: Hubert
authors.initials: H
authors.lastname: Wirtz
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D056809:Alveolar Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D011661:Pulmonary Stretch Receptors / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*
chemical_list: C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4
keywords: apoptosis; inflammation; lipopolysaccharide; lung injury; stretching